DESCRIPTION: In the Americas, from Mexico in the North to Argentina and Chile in the South, there are 16 to 19 million people infected with Trypanosoma cruzi, the causative agent of Chagas' disease. Estimated yearly incidence amounts to 561,000 cases not including countries like Argentina, Brazil, Chile and Uruguay where active programs of vector elimination have been in progress for years. It was estimated that 2 to 3 million individuals have the clinical symptoms that characterize the chronic stage of Chagas' disease, and that 45,000 of them die each year. Dr. Docampo's long-term goal is to find targets for the treatment of Chagas' disease. During the last granting period the major accomplishment has been the identification and characterization of an acidic organelle rich in calcium possibly involved in the regulation of Ca2+ and pH homeostasis in Trypanosoma cruzi that he named acidocalcisome. He also found that inorganic pyrophosphate and possibly a sugar pyrophosphate are apparently associated with these organelles. Inorganic pyrophosphate occurs in these parasites at concentrations higher than ATP. In addition, he found a "plant-like" enzymatic activity possibly associated with the same organelle in T. cruzi: a H+-translocating pyrophosphatase. These results could have important implications because the novel metabolic pathways identified in trypanosomes could be targets for chemo-therapeutic intervention. For the next granting period, he intends to focus on studying the acidocalcisomes with the following specific aims: specific aim 1: identification and characterization of the pyrophosphates present in acidocalcisomes; specific aim 2: characterization of T. cruzi H+-pyrophosphatase; specific aim 3: investigation of the role of acidocalcisomes in intracellular Ca2+ and pH homeostasis.